156 research outputs found
¿Influye el apoyo publicitario en el tiempo de aceptación del producto por parte del cliente?
During the worldwide pandemic many businesses started or significantly increased their online presence
on major e-commerce platforms either as vendors or as sellers. These small and medium businesses
need to understand what level of advertising support they need, if any, and how it can impact their
performance objectives. This paper investigates how advertising influences the timing of online customer
reviews after a product introduction at a major retailer with both physical stores and online e-commerce
presence open to both business sellers and vendors of various sizes. The faster time to reach customer
reviews is a proxy of customer product acceptance and should inform online businesses on their
advertising needs when they introduce their products on e-commerce platforms. This paper demonstrates
that without advertising support the time needed to reach ten customer reviews increases by 46%
gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway
Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER) and progesterone (PR) hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2), ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It also increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer
Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson’s disease
ABSTRACT: Impairments of action language have been documented in early stage Parkinson’s disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxelbased morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of
EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies
Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy
Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil
is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the
identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its
regulator, the non-coding pre-mir-nc886, have multiple e ects on cells in response to numerous types
of stress, including chemotherapy. In this work, we performed an ambispective study with 197
metastatic colon cancer patients with unresectable metastases to determine the relative expression
levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry
in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the
expression levels were related to the objective response to first-line chemotherapy following the
response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival
at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the
heterogeneity and complexity of oncological patients’ data. High expression levels of nc886 were
related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location
in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship
between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore,
this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to
establish clusters of patients depending on the cancer outcomes using algorithms for complex and
heterogeneous data.This research was funded by the Instituto de Salud Carlos III (DTS15/00174; PIE16-00045), by the
Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional
Development Fund (ERDF), references SOMM17/6109/UGR (UCE-PP2017-3) and (PI-0441-2014), and by the Chair
“Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963). This research was also funded partially
by RTI2018-098983-B-I00
Comparative Genome Analysis of Lactobacillus reuteri and Lactobacillus fermentum Reveal a Genomic Island for Reuterin and Cobalamin Production
Lactobacillus reuteri is a heterofermentative lactic acid bacterium that naturally inhabits the gut of humans and other animals. The probiotic effects of L. reuteri have been proposed to be largely associated with the production of the broad-spectrum antimicrobial compound reuterin during anaerobic metabolism of glycerol. We determined the complete genome sequences of the reuterin-producing L. reuteri JCM 1112T and its closely related species Lactobacillus fermentum IFO 3956. Both are in the same phylogenetic group within the genus Lactobacillus. Comparative genome analysis revealed that L. reuteri JCM 1112T has a unique cluster of 58 genes for the biosynthesis of reuterin and cobalamin (vitamin B12). The 58-gene cluster has a lower GC content and is apparently inserted into the conserved region, suggesting that the cluster represents a genomic island acquired from an anomalous source. Two-dimensional nuclear magnetic resonance (2D-NMR) with 13C3-glycerol demonstrated that L. reuteri JCM 1112T could convert glycerol to reuterin in vivo, substantiating the potential of L. reuteri JCM 1112T to produce reuterin in the intestine. Given that glycerol is shown to be naturally present in feces, the acquired ability to produce reuterin and cobalamin is an adaptive evolutionary response that likely contributes to the probiotic properties of L. reuteri
NMR Structures of Apo L. casei Dihydrofolate Reductase and Its Complexes with Trimethoprim and NADPH: Contributions to Positive Cooperative Binding from Ligand-Induced Refolding, Conformational Changes, and Interligand Hydrophobic Interactions
bS Supporting Information The enzyme dihydrofolate reductase (DHFR; 5,6,7,8-tetra-hydrofolate:NADPH oxidoreductase, EC 1.5.1.3) catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydro-folate (THF) using NADPH as coenzyme.1 Since THF and its metabolites are precursors of purine and pyrimidine bases, the normal functioning of this enzyme is essential for proliferating cells. This makes DHFR an excellent target for antifolate drugs such as methotrexate (anticancer), pyrimethamine (antimalarial), and trimethoprim (antibacterial). Such agents act by inhibiting the enzyme in parasitic or malignant cells.1,2 The cooperative binding of ligands to DHFR plays an important role not only in the enzyme catalytic cycle (negative cooperativity in THF/ NADPH binding)3 but also in enzyme inhibition (positive cooperativity in antifolate/NADPH binding).4 The effects of positive cooperative binding in controlling enzyme inhibition ar
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